Path Pt 2: Vulva, Vagina, Cervix Flashcards
smears of the inflammatory exudate from the active lesions show characteristic cytopathic changes consisting of multi-nucleated squamous cells containing eosinophilic to basophilic viral inclusions with a “ground glass” appearance
HSV
the infection is marked by acute inflammation of involved mucosal surfaces
- smears of exudate disclose phagocytosed gram-negative diplococci within neutrophils
- definitive dx requires culture or detection of gonococcal RNA or DNA
gonococcal
what happens when gonorrhea reaches the fallopian tubes?
acute suppurative salpingitis
- tubal mucosa becomes congested and diffusely infiltrated by neutrophil, plasma cells, and lymphocytes, resulting in epithelial injuryand sloughing of the plicae
- the tubal lumen fills with purulent exudate that may leak out of the fimbriated end
what happens if the gonorrhea infection spreads to the ovary?
salpingo-oophoritis
- collections of pus may accumulate within the ovary and tube (tubo-ovarian abscess) or tubal lumen (pyosalpinx)
what is chronic salpingitis?
scarring process that forms gland-like spaces and blind pouches
- the scarring of the tubal lumen and fimbriae may prevent the uptake and passage of oocytes, leading to infertility or ectopic pregnancy
this may develop as a consequence of the fusion of the fimbriae and the subsequent accumulation of the tubal secretions and tubal distention
hydropsalpink
compared to gonococcal infections, PID caused by what, tends to show less involvement of the mucosa and the tube lumen, and more inflammation within the deeper tissue layers
- these infections often spread throughout the wall to involve the serosa and the broad ligaments, pelvic structures and peritoneum
staph, strep and other puerperal invaders
what is a more frequent complication of strep or staph PID than of gonococcal infections?
bacteremia
presents either as a discrete white (hyperkeratotic) or a slightly raised, pigmented lesion
- microscopically: characterized by epidermal thickening, nuclear atypia, increased mitoses, and lack of cellular maturation
- analogous features to those seen in cervical squamous intraepithelial lesions
classic VIN
may be exophytic or indurated with central ulceration
- on histo: basaloid carcinoma consists of nests and cords of small, tightly packed cells that lack maturation and resemble the basal layer of the normal epithelium
- the tumor may have foci of central necrosis
VIN
what is characterized by exophytic, papillary architecture and prominent koilocytic atypia?
warty carcinoma
characterized by marked atypia of the basal layer of the squamous epithelium and normal-appearing differentiation of the more superficial layers
differentiated VIN
invasive what, that arise in differentiated VIN contain nests and tongues of malignant squamous epithelium with prominent central keratin pearls
keratinizing squamous cell carcinomas
distinctive intraepithelial proliferation of malignant cells
- these cells are larger than surrounding keratinocytes and are seen singly or in small clusters within the epidermis
- cells have pale cytoplasm containing mucopolysaccharide that stains with PAS, Alcian blue, or mucicarmine stains
Paget disease
what do Paget cells express?
cytokeratin 7
- they display apocrine, eccrine and keratinocyte differentiation and presumably arise from multi-potent cells found within the mammary-like gland ducts of the vulvar skin
approx 30% of vulvar cancers are caused by infection with high risk HPV’s, principally what strain?
- *16**
- these cancers develop from an in situ lesion termed classic vulvar intraepithelial neoplasia (classic VIN)
most vulvar cancers are not related to what?
HPV
- they develop in a background of lichen sclerosis or squamous cell hyperplasia from the premalignant lesion called differentiated vulvar intraepithelial neoplasia (differentiated VIN)
the diagnosis of what, is based on identification of nuclear atypia characterized by nuclear enlargement, hyperchromasia (dark staining), coarse chromatin granules, and variation in nuclear size and shape
squamous intraepithelial lesions (SIL)
the nuclear changes in SIL are often accompanied by what?
cytoplasmic “halos”, which consist of perinuclear vacuoles
what causes the cytoplasmic change in SIL?
HPV-encoded protein called E5 that localizes to the membranes of the endoplasmic reticulum
what is koilocytic atypia?
nuclear alterations with an associated perinuclear halo
the grading of SIL into low or high grade is based on expansion of what?
expansion of the immature cell layer from it’s normal, basal location
what would lead to a lesion graded as LSIL?
if the immature squamous cells are confined to the lower one third of the epithelium
what would lead to a lesion graded as HSIL?
if they expand to the upper two thirds of the epithelial thickness
the highest viral loads are found where in LSIL?
in maturing keratinocytes in the upper half of the epithelium
which proteins prevent cell cycle arrest?
HPV E6 and E7
- as a result, cells in the upper portion of the epithelium express markers of actively dividing cells, such as Ki-67, that are normally confined to the basal layer of the epithelium
what leads to over expression of p16, a cyclin-dependent kinase inhibitor?
disturbed growth regulation
both Ki-67 and p16 staining are highly correlated with what?
HPV infection and are useful for confirmation of the diagnosis in equivocal cases of SIL
this disease may manifest as either fungating (exophytic) or infiltrative masses
invasive cervical carcinoma
composed of nests and tongues of malignant squamous epithelium, either keratinizing or nonkeratinizing, which invade the underlying cervical stroma
squamous cell carcinoma of the cervix
characterized by a proliferation of glandular epithelium composed of malignant endocervical cells with large, hyperchromatic nuclei and relatively mucin-depleted cytoplasm, resulting in a dark appearance of the glands, as compared to the normal endocervical epithelium
adenocarcinoma
composed of intermixed malignant glandular and squamous epithelium
adenosquamous carcinoma
the type of carcinoma has as appearance similar to small cell carcinoma of the lung, but differs in being positive for high risk HPVs
neuroendocrine carcinoma
how does advanced cervical carcinoma spread?
by direct extension to contiguous tissues, including paracervical soft tissue, urinary bladder, ureters (resulting in hydronephrosis), rectum, and vagina
where would you find distant cervical carcinoma metastases?
liver, lungs, bone marrow, and other organs
what is the cervical cancer staging?
Stage 0 - CIS (CIN III, HSIL)
Stage I - carcinoma confined to the cervix
what stage is considered preclinical carcinoma, that is diagnosed only by microscopy?
Stage Ia
what stage of cervical carcinoma has stromal invasion no deeper than 3mm and no wider than 7mm (microinvasive carcinoma)
Ia1
what stage of cervical carcinoma has a maximum depth of invasion of stroma deeper than 3mm and no deeper than 5mm taken from base of epithelium; horizontal invasion not more than 7mm
Ia2
what stage of cervical carcinoma is histologically invasive carcinoma confined to the cervix and greater than stage Ia2?
Ib
what stage of cervical carcinoma extends beyond the cervix, but not to the pelvic wall?
- carcinoma involves the vagina but not the lower third
II
what stage of cervical carcinoma has extended to the pelvic wall?
- on rectal exam there is no cancer-free space between the tumor and the pelvic wall
- tumor involves the lower third of the vagina
III
what stage of cervical carcinoma has extended beyond the true pelvis or has involved the mucosa of the bladder or rectum
- this stage also includes cancers with metastatic dissemination
IV
productive HPV infections that usually regress spontaneously, but occasionally progress to high-grade squamous intraepithelial lesions (HSIL)
cervical low-grade squamous intraepithelial lesions (LSIL)
characterized by progressive deregulation of the cell cycle and increasing cellular atypia
- may progress to invasive carcinoma
HSIL
almost all cervical precursor lesions and cervical carcinomas are caused by high-risk HPV types, most commonly which?
16
